(1) Field of the Invention
The present invention relates to amino acid-based nutritional formulations.
(2) Description of the Related Art
Food allergy is an immunologically mediated clinical syndrome that may develop after the ingestion of a dietary product. The adverse reaction that accompanies a food allergy is often an immediate immunoglobulin-E (“Ig-E”) mediated reaction to dietary protein, otherwise known as a food protein allergy. Host, A., et al., Dietary Products Used in Infants for Treatment and Prevention of Food Allergy, Arch. Dis. Child 81:80-84 (1999). The spectrum of disorders caused by protein allergies is wide and may include angioedema, edema, atopic dermatitis, urticaria, eczema, asthma, rhinitis, conjunctivitis, vomiting, or anaphylaxis. Other reactions may be T-cell mediated and not associated with a specific IgE reaction, such as enterocolitis syndrome, proctocolitis, enteropathy, and a subset of allergic eosinophilic esophagitis/enteropathy.
Cow's milk allergy is the most common food protein allergy in young children and occurs in about 2% to 3% of all infants. Sampson, H. A., Food Allergy. Part 1: Immunopathogenesis and Clinical Disorders, J Allergy Clin. Immunol. 103:717-728 (1999). When certain infants are exposed to non-human milk, they can develop antibodies to foreign proteins found therein. Research has shown that potential allergens found in both milk- and soybean-based formulas are stable to digestion in the stomach for as long as 60 minutes (as compared to human milk protein which is digested in the stomach within 15 minutes). The foreign proteins then pass through the stomach and reach the intestines intact, where they gain access and can cause sensitization. The infant's immune system then “attacks” the foreign proteins, resulting in symptoms of an allergic reaction.
One possible explanation for the prevalence of protein allergies among infants is that intact cow's milk protein, which is found in most conventional infant formulas, is the earliest and most common food allergen to which infants and children are exposed. In fact, about 80% of formulas on the market are cow's milk-based.
Infant formulas and children's nutritional products have been designed to try to reduce the symptoms of protein allergies. One such formula is an extensively hydrolyzed cow's milk formula. Typically, the proteins in extensively hydrolyzed formulas have been treated with enzymes to break down some or most of the proteins that cause adverse symptoms with the goal of reducing allergic reactions, intolerance, and sensitization.
While extensive protein hydrolysates are less allergenic, they are not completely allergen-free. Halken S, et al., The Effect of Hypoallergenic Formulas in Infants at Risk of Allergic Disease, Eur. J. Clin. Nutr. 49(S1):S77-S83 (1995). Even residual peptides or small amounts of undigested protein may result in allergic symptoms. Further, the new protein structures created by the enzymes in hydrolyzed formulas may actually provoke an allergic response. Hudson M. J., Product Development Horizons—A View from Industry, Eur. J. Clin. Nutr. 49(S1):S64-S70 (1995). In fact, among children who are allergic to cow's milk, almost 10% are also sensitive to protein hydrolysate formulas. Giampietro P. G., et al., Hypoallergenicity of an Extensively Hydrolyzed Whey Formula, Pediatr. Allergy Immunol. 12:83-86 (2001).
Another alternative to cow's milk formula is a soy protein-based infant formula. Unfortunately, however, soy protein formulas can also cause allergies or intolerance reactions. In fact, about 8% to 14% of infants who are allergic to cow's milk are also allergic to the protein in soy formulas. Zeiger R. F., et al., Soy Allergy in Infants and Children with IgE-Mediated Cow Milk Allergy, J. Pediatr. 134:614-622 (1999). Infants with a previous history of cow's milk protein allergy or intolerance have a greater risk of developing soy protein allergy or intolerance, possibly due to the damage to the intestinal mucosa caused by cow milk proteins. This damage may allow an increased uptake of soy proteins, precipitating further reactions and symptoms.
Thus, for infants or children that have allergic reactions to hydrolyzed or soy-based products, a nutritional formulation based on amino acids is often the solution. Amino acids are the basic structural building units of protein. Breaking the proteins down to their basic chemical structure (completely pre-digested) makes amino acid-based formulas the most hypoallergenic formulas available. Commercially available amino acid based-formulas and nutritional supplements include Neocate®, EleCare®), and Vivonex® Pediatric.
For the infant or child that has multiple food protein intolerances or allergies, the amino acid-based nutritional formulation should contain an appropriate balance of amino acids. If possible, the ratios and amounts of amino acids in the nutritional formulation should mimic those found in breast milk. In addition, added constituents, such as emulsifiers, should avoid adding allergenic levels of protein to the formulation. From the foregoing, it can be seen that a need exists for an amino-acid based nutritional formulation which provides an appropriate balance of amino acids, includes an effective emulsification, and limits potentially allergenic levels of protein into the formulation via the emulsifying agent.